Toward adaptive radiotherapy for lung patients: feasibility study on deforming planning CT to CBCT to assess the impact of anatomical changes on dosimetry.

Changes in lung architecture during a course of radiotherapy can alter the planned dose distribution to the extent that it becomes clinically unacceptable. This study aims to validate a quantitative method of determining whether a replan is required during the course of conformal radiotherapy. The proposed method uses deformable image registration (DIR) to flexibly map planning CT (pCT) data to the anatomy of online CBCT images. The resulting deformed CT (dCT) images are used as a basis for assessing the effect of anatomical change on dose distributions. The study used retrospective data from a sample of seven replanned lung patients. The settings of an in-house, open-source DIR algorithm were first optimised for CT-to-CBCT registrations of the anatomy of the thorax. Using these optimised parameters, each patient's pCT was deformed to the CBCT acquired immediately before the replan. Registration accuracy was rigorously validated both geometrically and dosimetrically to confirm that the dCTs could reliably be used to inform replan decisions. A retrospective evaluation of the changes in dose delivered over time was then carried out for a single patient to demonstrate the clinical application of the proposed method. The geometric analysis showed good agreement between deformed structures and those same structures manually outlined on the CBCT images. Results were consistently better than those achieved with rigid-only registration. In the dosimetric analysis, dose distributions derived from the dCTs were found to match closely to the 'gold standard' replan CT (rCT) distributions across dose volume histogram and absolute dose difference measures. The retrospective analysis of serial CBCTs of a single patient produced reliable quantitative assessment of the dose delivery. Had the proposed method been available at the time of treatment, it would have enabled a more objective replan decision. DIR is a valuable clinical tool for dose recalculation in adaptive radiotherapy protocols for lung cancer patients.

Investigating the influence of intraindividual changes in perceived stress symptoms on injury risk in soccer.

Research has shown that high levels of stress and stress responsivity can increase the risk of injuries. However, most of the research that has supported this notion has focused on between-person relationships, ignoring the relationships at the within-person level. As a result, the objective of this study was to investigate if within-person changes in perceived stress symptoms over a 1-month time period could predict injury rates during the subsequent 3 months. A prospective design with two measurement points (Time 1-at the beginning of the season and Time 2-1 month into the season) was utilized. A total of 121 competitive soccer players (85 males and 36 females; Mage  = 18.39, SD = 3.08) from Sweden and the United States completed the Kessler Psychological Distress Scale (KPDS) and a demographic sheet at Time 1. The KPDS was also completed at Time 2, and all acute injuries that occurred during the subsequent 3-month period were recorded. A Bayesian latent change scores model was used to determine whether within-person changes in stress symptoms could predict the risk of injury. Results revealed that there was a credible positive effect of changes in stress symptoms on injury rates, indicating that an increase in reported stress symptoms was related to an increased risk for injury. This finding highlights the importance of creating caring and supportive sporting environments and relationships and teaching stress management techniques, especially during the earlier portion of competitive seasons, to possibly reduce the occurrence of injuries.

Drug Errors and Protocol for Prevention among Anaesthetists in Nigeria.

BACKGROUND: Drugs are often prescribed, dispensed, and administered by the same person during anaesthesia, and this may increase the risk of drug error. OBJECTIVES: To assess the frequency of drug administration errors by anaesthetists, the drugs commonly involved, and the effects of such errors. METHOD: A questionnaire-based study was carried out among participants at an annual conference of Nigerian anaesthetists. Sixty-six of the 80 participants returned the completed questionnaire. The respondents comprised 1 nurse anaesthetist, 34 resident doctors, 3 doctors with diploma in anaesthesia, and 28 consultant anaesthetists. The collated data on drug errors, the effect of such errors on patients, and formulated protocols to prevent future occurrence were subjected to descriptive analysis using Microsoft Excel. RESULT: Drug error was reported by 71.21% and witnessed by 22.72% of the respondents. Most of the drug errors occurred during general anaesthesia (90.3%) for emergency procedures (51.61%), and muscle relaxants were most commonly involved (58.06%). CONCLUSION: Drug errors are common among anaesthetists in Nigeria and their incidence is greater during general anaesthesia for emergency procedures, largely as a result of ampoule swaps due to similarities in ampoule design and packaging. Guidelines on their prevention should be developed by all health institutions.

Injuries in Swedish floorball: a cost analysis.

The epidemiology of sport injuries is well documented. However, the costs are rarely discussed. Previous studies have presented such costs in specific sports or localization. No study has investigated the costs related to injuries in elite floorball. Thus, the aim of this study was to estimate cost of injuries in Swedish elite floorball players. During 1 year, 346 floorball players were prospectively followed. All time-loss injures were recorded. The injured players were asked to complete a questionnaire regarding their costs tied to the injury. Mean costs were calculated by multiplying the total resource use with the collected unit costs and dividing these total costs with the number of injuries as well as players. The results showed that the average cost per injury increased with the level of severity and ranged from 332 to 2358 Euros. The mild and moderate overuse injuries were costlier than the corresponding traumatic injuries. However, the severe traumatic injuries were associated with higher costs than overuse injuries. Knee injuries were the costliest. Our results indicate that there are costs to be saved, if floorball injuries can be avoided. They should be of interest to decision makers deciding whether to invest in preventive interventions.

Psychological predictors of sport injuries among junior soccer players.

Previous researches have established models that specify psychological factors that could predict sport injuries. One example is Williams and Andersen's stress-injury model stressing factors such as anxiety, negative life stress and few coping resources. The purpose of the current study was to find psychological factors that could lead to an increased injury risk among junior soccer players, in addition to construct an empirical model of injury risk factors for soccer players. The participants were 108 male and female soccer players (m=17, 6) studying at soccer high schools in southwest Sweden. Five questionnaires were used, State Trait Anxiety Inventory, Sport Anxiety Scale, Life Events Survey for Collegiate Athletes, Athletic Coping Skills Inventory-28 and Swedish universities Scales of Personality. Injury record was collected by athletic trainers at the schools during a period of 8 months. The result suggested four significant predictors that together could explain 23% of injury occurrence. The main factors are life event stress, somatic trait anxiety, mistrust and ineffective coping. These findings partly support Williams and Andersen's stress-injury model and are organized into an empirical model. Recommendations are given to sport medicine teams and coaches concerning issues in sport injury prevention.

Factors influencing factor VIII activity in frozen plasma.

BACKGROUNDS AND OBJECTIVES: Fresh frozen human plasma is an important raw material in the production of coagulation factor concentrates used in patients with haemorrhagic disorders. The aim of the study was to determine how the handling of plasma influences the recovery of coagulation factor VIII activity (FVIII:C), i.e. the influence of time between donation and freezing, of the freezing time and of the ice front velocity. We also studied a tentative eutectic point in human plasma. MATERIALS AND METHODS: Aliquots of plasma from 12 different donors were kept at room temperature for 2, 4 and 6 h before start of freezing. We achieved fast freezing with a freezer that blows cooled air at a high velocity on the plasma containers. Freezing times were 0.5, 1, 4 and 24 h. Temperature was registered continuously during freezing. Plasma and NaCl solutions were frozen slowly to investigate the eutectic point. RESULTS: Storage at room temperature for 6 h caused a small but statistically significant decrease in FVIII:C. Slow freezing with programmed freezing times of 4 and 24 h caused a more pronounced drop in FVIII:C as compared to that of 30 and 60 min. We found no eutectic point in plasma or in plasma with addition of 2 % (w/v) NaCl. CONCLUSION: For an optimal yield of FVIII, freezing should start within 4 h after plasma donation. We propose the use of the term 'ice front velocity' instead of 'freezing speed', taking into consideration that the volume and shape of plasma containers may differ. We found only a marginal loss of FVIII:C when the ice front velocity was 26 mm/h or faster, but a significant loss when it was 9 mm/h or slower. We recommend freezing times of 60 min or shorter. We were not able to demonstrate any eutectic point in human plasma. We therefore recommend that the term eutectic point should not be used as a reference temperature in guidelines on plasma handling.

Dynamics of suspended sediment exchange and transport in a degraded mangrove creek in Kenya.

This study focuses on sediment exchange dynamics in Mwache Creek, a shallow tidal mangrove wetland in Kenya. The surface area of the creek is 17 km2 at high water spring. The creek experiences semidiurnal tides with tidal ranges of 3.2 m and 1.4 m during spring and neap tides, respectively. The creek is ebb dominant in the frontwater zone main channel and is flood dominant in the backwater zone main channel. During rainy season, the creek receives freshwater and terrigenous sediments from the seasonal Mwache River. Heavy supply of terrigenous sediments during the El Niño of 1997-1998 led to the huge deposition of sediments (10(60 tonnes) in the wetland that caused massive destruction of the mangrove forest in the upper region. In this study, sea level, tidal discharges, tidal current velocities, salinity, total suspended sediment concentrations (TSSC) and particulate organic sediment concentrations (POSC) measured in stations established within the main channel and also within the mangrove forests, were used to determine the dynamics of sediment exchange between the frontwater and backwater zones of the main channel including also the exchange with mangrove forests. The results showed that during wet seasons, the high suspended sediment concentration associated with river discharge and tidal resuspension of fine channel-bed sediment accounts for the inflow of highly turbid water into the degraded mangrove forest. Despite the degradation of the mangrove forest, sediment outflow from the mangrove forest was considerably less than the inflow. This caused a net trapping of sediment in the wetland. The net import of the sediment dominated in spring tide during both wet and dry season and during neap tide in the wet season. However, as compared to heavily vegetated mangrove wetlands, the generally degraded Mwache Creek mangrove wetland sediment trapping efficiency is low as the average is about 30% for the highly degraded backwater zone mangrove forest and 65% in the moderately degraded frontwater zone mangrove forest.

Anorectal irradiation in pelvic radiotherapy: an assessment using in-vivo dosimetry.

The objectives of this study were to measure by in-vivo techniques the radiation doses received by the anorectum during pelvic radiotherapy and compare these with doses predicted by a GE TARGET treatment planning system. Nine patients with cancers of the prostate, bladder, cervix or uterus were planned with computed tomography (CT) using the TARGET system. A Scanditronix rectal probe containing five n-type photon-detecting diodes was placed in the anorectum during the planning CT scans. The probe position was standardized with the five diodes at 2 cm intervals from the anal verge. The probe diodes were calibrated for 10 MV photons. Doses were measured for each diode for two consecutive fractions in the first four patients and for five consecutive fractions in the remaining five. Thermoluminescent dosimeters were used initially to verify diode doses. The TARGET and diode measured doses were compared. In all patients diodes situated in the target volume were within 7% of predicted doses. This improved to 2.5% after measurement on five fractions. At the edges of the target volume, wide variability existed between measured and predicted doses (measured dose range -68% to +68% of predicted dose). Outside the target volume, considerable doses (up to 0.3 Gy per fraction) were measured in the anal canal, which were not predicted by TARGET. We conclude that TARGET planned doses are accurate within the confines of the target volume. The greatest variability was seen at the edges of the target volume, where dose can vary by 50% across a 1 cm distance in the anterior-posterior plane. TARGET does not account for scattered dose beyond the field edges and therefore underestimates the dose received by the anal canal.

HLA-DR4 and salivary immunoglobulin A reactions to oral streptococci.

The aim of this study was to describe and compare salivary immunoglobulin A (IgA) antibody reactions to extracts of strains of three oral streptococci in human leukocyte antigen (HLA)-DR4-positive and -DR4-negative subjects. Whole paraffin-stimulated saliva samples were collected from 27 apparently healthy subjects. Previous HLA typing showed that 20 subjects were DR4 positive and 7 were DR4 negative. HLA-DRB1*04 subtyping was performed among the DR4-positive subjects. Whole-cell antigen extracts from Streptococcus mutans (KPSK 2), Streptococcus sobrinus (OMZ 65) and Streptococcus parasanguis (Nt 62) were separated in SDS-PAGE. The antigens were immunoblotted with diluted saliva (Western blot), scanned and analyzed in a computer system. All immunoblot bands were recorded in DR4-positive and DR4-negative saliva pools, and bands with an optical density >or=0.1 were selected for analysis in individual salivas. The DR4-negative subjects in general had more immunoblot bands and more distinct bands than did the DR4-positive subjects. A higher concentration of total IgA in saliva was correlated with more bands, especially to antigens separated from S. mutans. When the number of bands was calculated per IgA unit, significant differences were observed between DR4-positive and DR4-negative salivas. This was particularly seen for S. mutans and S. parasanguis. As the number of bands was analyzed in relation to DR4 subgroups, DRB1*04, there was a lower salivary IgA activity to S. mutans in the DRB1*0401 and *0404. The variable level of correlation previously demonstrated for S. mutans colonisation and serologically defined DR4 positive subjects might be explained by the heterogeneity in this group, and the relation should be sought on a subgroup level.

Evaluation of compensation in breast radiotherapy: a planning study using multiple static fields.

PURPOSE: A method that uses electronic portal imaging to design intensity-modulated beams for compensation in breast radiotherapy was implemented using multiple static fields in a planning study. We present the results of the study to verify the algorithm, and to assess improvements to the dosimetry. METHODS AND MATERIALS: Fourteen patients were imaged with computed tomography (CT) and on a treatment unit using an electronic portal imager. The portal imaging data were used to design intensity-modulated beams to give an ideal dose distribution in the breast. These beams were implemented as multiple static fields added to standard wedged tangential fields. Planning of these treatments was performed on a commercial treatment planning system (Target 2, IGE Medical Systems, Slough, U.K.) using the CT data for each patient. Dose-volume histogram (DVH) analysis of the plans with and without multileaf collimator (MLC) compensation was carried out. This work has been used as the basis for a randomized clinical trial investigating whether improvements in dosimetry are correlated with the reduction of long-term side effects from breast radiotherapy. RESULTS: The planning analysis showed a mean increase in target volume receiving 95-105% of prescribed dose of 7.5% (range -0.8% to 15.9%) when additional MLC compensation was applied. There was no change to the minimum dose for all 14 patient data sets. The change in the volume of breast tissue receiving over 105% of prescribed dose, when applying MLC compensation, was between -1.4% and 11.9%, with positive numbers indicating an improvement. These effects showed a correlation with breast size; the larger the breast the greater the amount of improvement. CONCLUSIONS: The method for designing compensation for breast treatments using an electronic portal imager has been verified using planning on CT data for 14 patients. An improvement was seen in planning when applying MLC compensation and this effect was greater the larger the breast size.

HLA-DR4 and number of mutans streptococci in saliva among dental students and staff.

Our aim was to corroborate previous findings that HLA-DR4 carriers are characterized by higher levels of mutans streptococci in saliva than are individuals expressing other HLA-DR types. Of 68 subjects (dental students, staff, and faculty) who were sampled for salivary counts of mutants streptococci, 13 subjects with the lowest counts of mutans streptococci and 15 subjects with the highest counts were selected for HLA-typing. Of the 13 who expressed HLA-DR4, 8 were heavily colonized by mutants streptococci. Although a trend towards a relationship was found between HLA-DR4 carriage and high levels of mutans streptococci, it was not statistically significant. In this selected population, knowledge of how to minimize the risk of caries and mutans streptococci level may have influenced the results.

HLA DRB1* typing and cartilage oligomeric matrix protein (COMP) as predictors of joint destruction in recent-onset rheumatoid arthritis.

The carriage of a characteristic sequence of amino acids at position 67-72 in the third hypervariable region of the HLA DRB1 chain has been linked to susceptibility to rheumatoid arthritis (RA). Whether this epitope is also a predictor of more severe disease remains controversial. Cartilage oligomeric matrix protein (COMP) is a protein, the serum levels of which have been found to correlate with large joint destructive disease in previous work. In this paper, we compare DRB1* typing and serum COMP levels in a prospectively observed group of RA patients with or without early hip joint destruction. The COMP levels at study inclusion, median 11 months from onset of symptoms, were significantly higher in the patients with early hip joint destruction compared to the patients in the more benign group. There was no difference in the number of disease susceptibility-related epitopes between the groups. DRB1*04, in contrast, was found among 8/8 patients with hip destruction, but also in 5/8 more benign cases. We conclude that in this type of RA patient, COMP serum levels are more informative predictors of aggressive disease than HLA DRB1* typing.

Coping strategies among long-term injured competitive athletes. A study of 81 men and women in team and individual sports.

Differences in personality, mood and coping ability between athletes of a high competitive level with long-term injuries (n = 81), with a mean age of 24.4 years, and a matched non-injured group (n = 64), with a mean age of 24.2 years, were investigated. Three self-rating scales were employed: mood adjective check-list, general coping questionnaire and Karolinska scales of personality. Although no differences in basic personality traits were found, being injured was found to result in a depressed mood state and in the activation of coping strategies directed at receiving help. Comparisons were made between injured male and female athletes as well as between team-sport and individual-sport athletes. Women were found to become more anxious and tense and to have a stronger inclination to use emotion-focused coping strategies. Team-sport athletes were found to cope more in terms of 'passive acceptance' of help from others, whereas individual athletes were found to activate 'problem-solving' strategies in face of a stressor. The results suggest that social aspects of rehabilitative work are important and support the concept that rehabilitative work with long-term injured athletes should be individualized to be maximally effective. They also support the usefulness of cognitive models of the injured athlete's experience of being long-term injured. Such models, however, do not account for differences between the sexes or between individual and team athletes.

Development of radiographic damage during the first 5-6 yr of rheumatoid arthritis. A prospective follow-up study of a Swedish cohort.

The objective of this study was to describe the development of radiographic damage in patients with RA and to search for predictors of radiographic progression over 5 yr. One hundred and thirteen patients, 75 female and 38 male, mean age 53 yr, with definite RA and mean disease duration of 11.4 months, were followed prospectively for 5 yr at an out-patient clinic. Radiographs of the hands and feet were performed annually, and evaluated according to Larsen. The predictive value of demographic, clinical and laboratory variables at study start was evaluated. A stepwise logistic regression model was applied. We found that radiological joint damage occurred early and was significantly progressive during the 5 study years. The rate of progression was most prominent during the first 2 yr. At study start, 53% of the patients had no detectable erosions, but only 11% remained non-erosive. Twenty-six per cent of the patients with the initial presence of erosions did not progress substantially and needed no aggressive therapy. High joint damage progression during the first year, female gender and high baseline ESR could predict 57% of the patients with high total radiographic progression. Age, disease duration, rheumatoid factor, genetic factors, active joint count and the presence of erosions at study start had no predictive value.

Associations of HLA-DRB and -DQB genes with two and five year outcome in rheumatoid arthritis.

OBJECTIVE: To evaluate the clinical usefulness of genomic HLA typing during the first five years of established rheumatoid arthritis (RA). METHODS: The HLA-DRB and -DQB alleles were determined by restriction length polymorphisms and polymerase chain reaction amplification with sequence specific primers in 99 Swedish patients with RA. Clinical features after two and five years disease duration were related to the genetic pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patients were in remission after five years. Disability was assessed by health assessment questionnaire, and radiographic damage in hands and feet by the Larsen method. RESULTS: Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one allele, and 26% had DRB1*04 on both alleles (all frequencies significantly greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and *0302 were normal. Patients carrying DRB1*04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disability did not vary with regard to the genotype. Homozygous HVR3 patients had about three times greater risk of undergoing joint replacement. Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with erosive disease. CONCLUSIONS: We confirmed a strong association of disease with the presence of the shared epitope on one or two alleles. However, genotype was not strongly associated with disease severity after two and five years disease duration, and thus the value of genomic typing to select patients for early aggressive therapy is questionable.

HLA frequency in patients with chronic secretory otitis media.

It is well established that relationships exist between the frequencies of certain HLA antigens and various disease entities. In an earlier study we found a significant correlation between the frequency of HLA-A2 and HLA-A3 and recurrent acute otitis media (rAOM). Of 34 HLA antigens analysed, HLA-A2 occurred in 80.0% and HLA-A3 in only 11.1% of children with rAOM as compared to 55.9% and 27.5%, respectively, in healthy controls. In the present study we investigated the frequencies of the same 34 HLA antigens in 40 children who had been regularly controlled at our clinic for chronic secretory otitis media (SOM) for at least 6 years. HLA-A2 was found in 52.0% (21/40) and HLA-A3 in 27.5% (11/40) of these children, figures on a par with those of healthy controls. The HLA-A2 frequency was significantly lower in chronic SOM patients than in rAOM children. Some other non-significant differences were also found between these two groups. The results indicate a difference in hereditary influence on the pathogenesis of rAOM and that of chronic SOM.

HLA-DR antigens, Gm allotypes and antiallotypes in early rheumatoid arthritis--their relation to disease progression.

OBJECTIVE: Evaluation of the prognostic value of immunogenetic markers in early rheumatoid arthritis (RA). METHODS: Ninety-nine patients with definite RA and disease duration 24 months or less were followed with standardized assessment. Disability was assessed by the HAQ index and radiographic changes in hands and feet by the Larsen method. The frequencies of HLA-DR genes were determined by serological typing, Gm allotype distribution by classical hemagglutination inhibition test, and occurrence of anti-Gm allotypes by use of anti-Rh coats. The immunogenetic findings were related to disease severity after 2 years' followup. RESULTS: Functional capacity was well preserved, disease activity was less, but radiographic changes in hands and feet had increased considerably at study finish. A group of 13 patients had developed rapidly progressive changes of hip and/or shoulder joints, all requiring arthroplasty. There was a significantly increased frequency of HLA-DR4. Twenty-seven of the 68 HLA-DR4 positive patients were putatively homozygous. HLA-DR4 was not related to disability or to severe small joint destruction. However, progressive large joint damage was significantly more prevalent in homozygous patients (p < 0.01). Gm allotype distribution was normal and not related to clinical findings. Anti-Gm antibodies were common and frequently specific for nonhost Gm allotype. Fifty-six patients carried anti-G1m(a), and occurrence of this antibody was significantly associated with radiographic progression of small joints (p = 0.01), presence of nodules (p < 0.01) and number of active joints (p = 0.001). CONCLUSION: Immunogenetic markers aided in identifying patients with early RA with more severe disease.

HLA antigens and recurrent acute otitis media.

The frequencies of a number of HLA antigens were investigated in 45 individuals with clinical recurrent acute otitis media (rAOM), defined as six or more episodes of AOM during a 12-month period, and were compared to those in a control group from the same district. HLA-A2 was found to occur in 80% of the rAOM group, as compared to 55.9% of controls (p less than 0.01). HLA-A3 antigen occurred in only 11.1% of the rAOM group in contrast to 27.5% of controls (p less than 0.05). Among 22 prospectively followed children without any AOM during their first 3 years of life, the frequencies of HLA-A2 and HLA-A3 antigens were comparable with those among controls.